ATLA::Alternatives to Laboratory Animals

Volume 30, Number 2

Losartan decreases glomerular filtration rate in isolated perfused porcine slaughterhouse kidneys.

Katja Stahl,¹ Claudia Fehrenberg,¹ Evelyn Neew-Galuschka,² Thomas Krössin² And Gabriele Kaczmarczyk²

¹Tierexperimentelle Einrichtung and ²Experimentelle Anästhesie, Campus Virchow Klinikum, Charité, Augustenburger Platz 1, 13353 Berlin, Germany

SUMMARY

We investigated whether Losartan, an angiotensin II (Ang II) AT₁ receptor antagonist, decreases renal vascular resistance (RVR) and increases glomerular filtration rate (GFR) in isolated perfused porcine slaughterhouse kidneys (11 control experiments and 11 Losartan experiments with 7.5 mg Losartan in the preservation solution and 100 µg/minute Losartan infused during perfusion). With perfusion, plasma renin activity (PRA) increased markedly from 3 ± 1 to 90 ± 17 ng Ang l/ml/h (control), and from 4 ± 1 to 70 ± 8 ng Ang l/ml/h (Losartan), plasma Ang II increased from 86 ± 63 to 482 ± 111 pg/ml (control), and from 73 ± 42 to 410 ± 91 pg/ml (Losartan). The GFR was decreased in Losartan experiments as compared with control experiments (5 ± 1 versus 10 ± 2 ml/min/lOO g kidney wt; p < 0.05). The RVR was the same in both groups (0.2 ± 0.01 mm Hg/1OO g kidney wt/min/ml). Tubular sodium reabsorption was decreased in Losartan experiments as compared with control experiments (0.7 ± 0.1 versus 1.4 ± 0.3 mmol/min/100 g kidney wt). Overall, Losartan accentuated pathophysiological signs of acute renal failure. Although other drugs have to be investigated, these results suggest that porcine slaughterhouse kidneys could be useful as a tool for research in areas such as transplantation and intensive-care medicine.

Keywords: efferent arteriole, isolated perfused kidneys, renal transplantation, renin-angiotensin-system